Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of nigrostriatal dopaminergic neurons. The cause of this degeneration has yet to be fully understood. However, there is increasing evidence that PD is the result of a complex set of interactions encompassing genetic predisposition, the innate oxidative characteristics of the nigrostriatal dopaminergic pathway and inflammation. Less than 10% of PD cases are hereditary. A subset of which has been linked to two mutations in the alpha-synuclein gene. Our laboratory has obtained a mouse that over-expresses human alpha-synuclein under the control of the platelet-derived growth factor promoter. Using this mouse as a genetic model of PD, I plan to examine the inflammatory mechanisms leading to the loss of nigrostriatal dopaminergic neurons after exposure to the inflammagen lipopolysaccharide (LPS). I hypothesize that in the context of increased alpha-synuclein expression, inflammation is detrimental to dopaminergic neurons. Furthermore, I hypothesize that LPS mediated inflammation will result in the loss of dopaminergic cells in the substantia nigra of the alpha-synuclein over-expressing murine model of PD. [unreadable] [unreadable]